Discussion

In our case, an 18-year-old woman presented with recurrent fever, claudication of limbs, postprandial abdominal pain, a difference of >10 mm Hg in systolic blood pressure between arms and bruits that could be heard along both the carotid and subclavian arteries. These were caused by the narrowing of the subclavian artery and the abdominal aorta and reflected end-organ ischaemia. Even without arteriography, the clinical findings in our patient met four out of six TA criteria defined by the American College of Rheumatology.1 3 5 6 The presence of three or more out of the six criteria is known to have a sensitivity of 90.5% and specificity of 97.8%.5 6 Our patient also met all the clinical criteria European League Against Rheumatism/Pediatric Rheumatology International Trials Organization/Pediatric Rheumatology European Society criteria for childhood TA, which has a sensitivity and specificity of 100% and 99.9%.6 7 TA was then suspected, and the narrowing of the blood vessel was then confirmed by digital subtraction arteriography and duplex ultrasound done in the tertiary hospital.

Differential diagnoses, in this case, include other primary vasculitides, which can manifest as constitutional symptoms, joint pain and muscle weakness. These vasculitides include giant cell arteritis, polyarteritis nodosa, Henoch-Schonlein purpura, granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Giant cell arteritis usually manifests in older women and can be ruled out due to the early age of onset of the disease.8 Polyarteritis nodosa usually manifests as renal insufficiency, neuropathy, with alternating microaneurysm and constriction of the affected blood vessels in arteriography.9 The absence of renal insufficiency, neuropathy and imaging findings rules out this disease. Henoch-Schonlein purpura is a small vessel vasculitis that usually affects children. It manifests as palpable purpura on the lower half of the body and glomerulonephritis, the absence of which rules out the disease.10 Microscopic polyangiitis and GPA are small to middle size vessel vasculitides that usually manifest as haematuria and haemoptysis.11 EGPA is similar to GPA with the addition of >10% eosinophilia and a history of asthma.12 These three vasculitides are known for their association with positive serum antineutrophilic antibodies (ANCA).11 12 While a test for serum ANCA was not available in our hospital, our patient did not have the usual findings attributed to these diseases, such as skin lesion, haemoptysis and renal insufficiency. None of the vasculitides mentioned above has a discrepancy of blood pressures between the right and the left arm as a clinical finding.8–12

In our patient, the disease affected both the superior branches of the aorta, as supported by the physical examination, and the abdominal aorta, with the highest degree of stenosis in the abdominal aorta. This clinical presentation matches type V TA, as classified in the Takayasu Conference in 1994.1 3

The treatment for TA consists of immunosuppressant therapy. High-dose corticosteroid is the mainstay of the therapy, although tapering of the dose can sometimes cause relapses of the disease. It is recommended to add a second immunosuppressive agent such as methotrexate, cyclosporine A, tacrolimus, azathioprine, cyclophosphamide and mycophenolate mofetil.3 13 14 In this patient, diltiazem is also added to manage hypertension.

Multiple studies have shown the benefit of stenting or surgery to correct severe stenosis.14 15 Indications for surgery include uncontrolled hypertension as a consequence of renal artery stenosis, severe symptomatic coronary artery or cerebrovascular disease, severe aortic regurgitation or coarctation, stenotic or occlusive lesions resulting in critical limb ischaemia and aneurysms at risk of rupture.15

As noted above, TA is a disease of chronic granulomatous inflammation of the aorta or its branches. This inflammation will eventually cause fibrinoid necrosis, and fibrosis, narrowing and aneurysm of the vessel wall.1 13 TA manifestation can be divided into two phases: an initial phase of unspecific findings, for example, fever, malaise and headache, and a late stenotic phase characterised by findings such as hypertension, claudication, pulselessness, bruit and angina.1 13 14 16 17 If left untreated, TA will eventually cause irreversible target organ damage and severe morbidity.

The diagnosis of TA has always been a challenge. Multiple case reports and studies have shown that the diagnosis of TA is usually delayed 10 months to 12 years, with 91% of patients reporting having seen at least one physician before diagnosis.15 18 19 By the time of diagnosis, the patient usually has already suffered significant morbidity. In our case, the diagnosis was delayed by 2 years. However, the disease may have existed for a longer period since it cannot be ascertained whether the patient’s childhood hypertension had been a result of TA progression.

This delay of diagnosis can be attributed to a few factors. First, both the early and late manifestation of TA is not specific.17 19 Laboratory findings include acute-phase reactant markers or ESR, which are not specific for TA.13–15 18 The advent of non-invasive imaging modalities, for example, MR arteriography (MRA), CT angiography (CTA) and positron emission tomography with ¹⁸F-FDG (FDG-PET), have helped diagnose TA even in the prestenotic phase.15 18–20 FDG-PET is a functional imaging tool that can detect inflammation in the vessel wall and has a demonstrated pooled sensitivity of 87% and specificity of 73% for the assessment of TA. MRA and CTA are usually used in conjunction with FDG-PET to detect structural changes and complications.20 These tools, however, are not readily available in rural hospitals. They are also very expensive and are not covered by the Indonesian government health insurance programme, which is the primary method of payment used in rural areas. Therefore, the most crucial factor of early diagnosis is the physician’s awareness of the clinical findings.15 18 19

Although not specific, duplex ultrasound can provide evidence of stenosis in the arteries affected by TA.21 In our patient, duplex ultrasound performed in the tertiary hospital showed stenosis in the right common carotid artery with increased intimamedial thickness (figure 2). The classic finding of TA in ultrasound is stenosis with a homogeneous hypoechoic circumferential thickening of the intimamedia complex, also known as the macaroni sign. This finding is absent in our patient, most likely due to the ultrasound being performed after months of treatment.

Another cause of delay in this patient lies in the unfamiliarity of physicians with the disease.18 19 Indonesia is a tropical country and is endemic to many infectious diseases, such as enteric fever. Therefore, it is more likely that infectious disease is suspected first in a patient with fever.22 Another cause of unfamiliarity with TA is the rarity of the disease and the lack of case reports or studies about TA in Indonesia.

Since the most important factor for early diagnosis of TA is the physician’s awareness of the findings, Nazareth and Mason proposed ‘red flag’ signs and symptoms that should direct physicians’ suspicion to TA (box 1).18 In this patient, seven out of nine findings were found in our patient.